This proposal responds to the Genes, Environment, and Development Initiative (RFA-DA-07-012) to examine the interplay of genes and environment in the development of longitudinal patterns of substance use disorders and comorbid problems from early adolescence through mid-adulthood. To this end, we have assembled an interdisciplinary team including specialists in behavioral, molecular, and statistical genetics, human development, sociology, psychology, and the development of substance use disorders and delinquency, to analyze data from two studies selected for different strengths: a national probability sample of households (National Youth Survey, Institute of Behavioral Science, University of Colorado, Boulder) and a high-risk urban community sample (Seattle Social Development Project, Social Development Research Group, University of Washington). Each study provides over 20 years of longitudinal data on environmental influences on the development of substance use, abuse and dependence, and delinquency from early adolescence to mid-adulthood. Both studies include DSM-IV diagnoses as well as other categorical and quantitative measures of substance abuse and related phenotypes of demonstrated heritability. Investigators on these two studies are joined by members of the Institute for Behavioral Genetics (University of Colorado, Boulder), a leading center for behavioral genetic studies in the US, who have a history of successful collaboration with the National Youth Survey and other national longitudinal studies of health and behavior. The development of substance use disorders has been associated with family, peer, school and community predictors during the life course, as well as with genetic polymorphisms in the dopamine, serotonin and drug metabolism systems. The proposed study will (1) collect blood samples from both SSDP and NYS to provide DNA data to the NIDA genetics consortium as well as to the two studies;(2) genotype existing and new DNA samples using dense SNP coverage of targeted genes;and (3) examine the gene-environment interplay in the development of SUD and comorbid problems.